Increased expression of CD133 and reduced dystroglycan expression are strong predictors of poor outcome in colon cancer patients

Abstract

BackgroundExpression levels of CD133, a cancer stem cell marker, and of the α-subunit of the dystroglycan (α-DG) complex, have been previously reported to be altered in colorectal cancers.MethodsExpression levels of CD133 and α-DG were assessed by immunohistochemistry in a series of colon cancers and their prognostic significance was evaluated.ResultsScattered cells positive for CD133 were rarely detected at the bases of the crypts in normal colonic mucosa while in cancer cells the median percentage of positive cells was 5% (range 0–80). A significant correlation was observed with pT parameter and tumor stage but not with tumor grade and N status. Recurrence and death from disease were significantly more frequent in CD133-high expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor groups for both disease-free (p = 0.002) and overall (p = 0.008) survival.Expression of α-DG was reduced in a significant fraction of tumors but low α-DG staining did not correlate with any of the classical clinical-pathological parameters. Recurrence and death from the disease were significantly more frequent in α-DG-low expressing tumors and Kaplan-Meier curves showed a significant separation between high vs low expressor tumors for both disease-free (p = 0.02) and overall (p = 0.02) survival. Increased expression of CD133, but not loss of α-DG, confirmed to be an independent prognostic parameters at a multivariate analysis associated with an increased risk of recurrence (RR = 2.4; p = 0.002) and death (RR = 2.3; p = 0.003).ConclusionsLoss of α-DG and increased CD133 expression are frequent events in human colon cancer and evaluation of CD133 expression could help to identify high-risk colon cancer patients.

CD133/CD166/Ki-67 Triple Immunouorescence Assessment for Putative Cancer Stem Cells in Colon Carcinoma*

“…us, the rate of CD133-positive staining was reported to be between 15.3-91.4% [6,14,18,19,21,22,41], while for CD166, CRC reactivity varied between 34 and 76% [14,33,34]. e prevalent tumour staining pattern for CD133 in our study was cytoplasmic, while for CD166 it was mainly membranous-like, which is in accordance with previously reported results [6,14,21,22,33,42].…”

“…CD133 expression in the non-neoplastic colon mucosa was weak compared with dysplastic and neoplastic tissues, and was mostly present in the cells from the base of the crypts, similar to the results of previous studies [6,14,18]. e most common expression pattern found was a cytoplasmic dot-like staining, with a less spread membranous-like pattern.…”

“…During the last decade, many CSC surface markers were proposed, including CD133 and CD166 [12][13][14]. Inconsistent data exist regarding the prognostic significance of these markers' expression in CRC [14,18,22,[32][33][34]. us, we aimed to investigate the immunoexpression patterns of CD133 and CD166 in colon carcinoma, both individually and in combination, in order to assess their signi cance as prognostic markers.…”

“…23 No 2: 161-170 [17]. In addition, several studies have evidenced that CD133 expression may serve as an independent marker for prognosis and chemoresistance in CRC [7,[18][19][20][21]. However, other authors have failed to establish a correlation between CD133 expression and tumour progression or survival [14,22], making thus questionable its predictive value in CRC.…”

“…Some authors proposed that apical/endoluminal membranous CD133 staining is a characteristic of well oriented, polarized and di erentiated cells, while cytoplasmic staining may be indicative of putative CSCs [44,45]. ese large discrepancies have been attributed mainly to methodological variations and di erent scoring systems [18,46,47]. It seems that only membranous CD133 overexpression correlates with patient survival times, recurrence-free survival times and chemoresistance [21,48].…”